DIetary REstriction as an Adjunct to Neoadjuvant ChemoTherapy for HER2 Negative Breast Cancer (DIRECT)

Leiden University Medical Center (LUMC)

Status and phase: Completed; Phase 3; Phase 2

Conditions: Breast Cancer; Neoadjuvant Chemotherapy; Fasting Mimicking Diet; Pathological Complete Response

Treatments: Other: Fasting mimicking diet

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT02126449

p13.135 (Other Identifier)

BOOG2013-04 (Other Identifier)

NL44684.058.13

Details and patient eligibility

About

Preclinical studies provide strong support for the concept that fasting evokes resistance to multiple forms of stress. Fasting reduces plasma levels of growth factors and modulates intracellular nutrient sensing systems, thereby diverting energy from growth to maintenance. Accordingly, the currently available preclinical evidence suggests that short-term fasting protects normal cells against the perils of chemotherapy. In contrast, cancer cells are not protected, as a result of their self-sufficiency in growth signals. This phenomenon is termed Differential Stress Resistance (DSR). DSR reduces the severity of toxic side-effects of chemotherapy and interestingly, it simultaneously renders cancer cells more vulnerable to chemotherapeutics. Importantly, extensive preclinical evidence and preliminary clinical data indicate that a specifically designed very low calorie, low amino acid substitution diet ("Fasting Mimicking Diet, FMD") has effects on cancer therapy that are very similar to those of fasting. This study aims to evaluate the impact of the FMD on tolerance to and efficacy of neoadjuvant chemotherapy in women with stage II or III breast cancer.

Enrollment: 131 patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female patients with stage II or III (cT1cN+ or ≥T2 any cN, cM0) breast cancer receiving neoadjuvant AC-T
• Measurable disease (breast and/or lymph nodes)
• HER2 negative core biopsy Age ≥18 years
• WHO performance status 0-2
• Adequate bone marrow function : white blood cells (WBCs) ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
• Adequate liver function: bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL
• Adequate renal function: the calculated creatinine clearance should be ≥50 mL/min
• Patients must be accessible for treatment and follow-up
• Written informed consent according to the local Ethics Committee requirements
• Willing to fill in quality of life questionnaires
• Able to read and write in Dutch

Exclusion criteria

• History of breast cancer (invasive or non-invasive)
• Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
• Serious other diseases such as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias
• Diabetes Mellitus
• Body mass index (BMI) < 19 kg/m2
• Pregnancy or lactating
• Significant food allergies which would make the subject unable to consume the food provided (ex: nuts or soy)
• Any metabolic disorders that may affect gluconeogenesis or adaptation to short fasting periods.
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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131 participants in 2 patient groups

Fasting mimicking diet

Experimental group

Description:

Short term fasting using Fasting mimicking diet around neoadjuvant chemotherapy (AC\>T)

Treatment:

Other: Fasting mimicking diet

regular diet

No Intervention group

Description:

Standard neoadjuvant chemotherapy (AC\>T)